Field of the Invention
This invention is in the field of X-ray laser microscopy.
Description of the Related Art
The resolving power of conventional optical microscopes is limited by the wavelength of light. Thus over the years, various methods employing shorter wavelength particles, such as electrons, and shorter wavelength photons, such as X-rays, have been employed to achieve still higher levels of resolution.
X-ray radiation spans a range of wavelengths in the nanometer region, generally ranging from about 10 nanometers (soft X-rays) with energies of around 100 electron volts, to about 0.01 nanometers (hard X-rays) with energies up to about 10,000 electron volts. Photons with energies above this are typically referred to as gamma rays. Since many molecular biological structures of interest have structural details in roughly the 10 to 0.1 nanometer range, scientists have turned to X-rays to help elucidate the structure of proteins, DNA, membranes, viruses, cells, and other biological structures of interest.
Due to the desirable aspects of coherent light sources, X-ray lasers are particularly useful for X-ray microscopy. Here various methods have been employed, including X-ray diffraction methods, X-ray holographic methods, and various types of X-ray imaging methods. Although X-ray mirrors and lenses are much more difficult to fabricate than their optical counterparts, various methods of focusing X-rays, including Wolter, Kirkpatrick-Baez, and Schwarzschild x-ray mirror designs, as well as various types of zone plate methods (which operate according to diffraction methods) have been devised.
Some recent improvements in zone plate technology include the work of Chang and Sakdinawat, “Ultra-high aspect ratio high-resolution nanofabrication for hard X-ray diffractive optics” NATURE COMMUNICATIONS, 5:4243, Jun. 27, 2014, pages 1-7 (DOI: 10.1038/ncomms5243). They taught that improved zone plates can be produced using some of the same photolithographic methods used to produce modern integrated circuits and other nanostructures. These methods are also described by their US patent application 2015/037679.
Previous work in the X-ray microscopy field includes the soft X-ray imaging methods of Suckwer et. al., U.S. Pat. No. 5,177,774; Chao et. al, “Soft X-ray microscopy at a spatial resolution better than 15 nm”, NATURE, Vol 435, Jun. 30, 2005, pages 1210 to 1213; and Kirtz et. al., “Soft X-ray microscopes and their biological applications”, Q. Rev. Biophys. 28, 33-130 (1995).
Other workers have used ultra-short bursts of hard X-rays, often produced by free electron lasers, and X-ray diffraction methods, to elucidate structures at still higher resolution. This work includes Gaffney et. al., “Imaging Atomic Structure and Dynamics with Ultrafast X-ray Scattering”, Science 316, Jun. 8, 2007, pages 1444-1448.
Despite these advances, the field remains challenging. The highest resolution laser microscopy sample details can generally only be obtained by using ultra-short hard X-rays, which are difficult to focus, and which tend to rapidly destroy the sample. Here, use of X-rays produced by free electron lasers, ultra-short bursts of energy, and X-ray diffraction methods (which do not require the sample scattered X-rays to be imaged) are favored.
By contrast, lower resolution laser microscopy, using soft X-rays, is a bit closer to conventional microscopy. Coherent soft X-ray light can be produced by a variety of different methods, and the lower energies tend to be less destructive of the sample. The soft X-rays, after being scattered by the sample, can be focused by various methods, such as various phase zone plate methods, resulting in a more conventional type magnified image of the sample.
Another problem is that the performance of existing X-ray laser microscopes can be limited by other effects, such as X-ray scattering or attenuation off of residual air molecules in the vacuum chamber, and by thermal effects (e.g. heating of the sample and X-ray lenses).
Another problem is sample administration. Although some prior art methods, such as the methods of Gaffney, are configured to analyze more than one sample by sending particle stream composed of a plurality of single particles through the X-ray beam, such methods can have drawbacks.